Anti-VEGF Drugs Dynamics: Relevance for Clinical Practice

Daniele Veritti; Valentina Sarao; Gianluca Gorni; Paolo Lanzetta

doi:10.3390/pharmaceutics14020265

Anti-VEGF Drugs Dynamics: Relevance for Clinical Practice

Pharmaceutics. 2022 Jan 23;14(2):265. doi: 10.3390/pharmaceutics14020265.

Authors

Daniele Veritti¹, Valentina Sarao^{1

2}, Gianluca Gorni³, Paolo Lanzetta^{1

2}

Affiliations

¹ Department of Medicine-Ophthalmology, University of Udine, 33100 Udine, Italy.
² Istituto Europeo di Microchirurgia Oculare (IEMO), 33100 Udine, Italy.
³ Department of Mathematics and Computer Science, University of Udine, 33100 Udine, Italy.

Abstract

Background: A drug and disease assessment model was used to evaluate the impact of different treatment regimens on intravitreal ranibizumab, bevacizumab, aflibercept, and brolucizumab concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF.

Methods: A time-dependent mathematical model using Wolfram Mathematica software was used. The pharmacokinetic and pharmacodynamic data for anti-VEGFs were obtained from published reports. The model simulated drug concentration after single and multiple doses of ranibizumab, bevacizumab, aflibercept, and brolucizumab, and it extrapolated time-dependent intraocular free VEGF proportion values. Various fixed treatment regimens (q4, q8, q10, q12) were simulated and evaluated as candidates for clinical utilization.

Results: Our mathematical model shows good correlation between intraocular VEGF proportion values and clinical data. Simulations suggest that each anti-VEGF agent would allow for distinct treatment intervals to keep the proportion of free VEGF under threshold levels. Regimens scheduling q8 ranibizumab, q8 bevacizumab, q12 aflibercept, and q10 brolucizumab administration permit to maintain the proportion of unbound VEGF below 0.001%.

Conclusions: Fixed q8 ranibizumab, q8 bevacizumab, q12 aflibercept, or q10 brolucizumab regimens may produce adequate intraocular VEGF inhibition.

Keywords: aflibercept; age-related macular degeneration; bevacizumab; brolucizumab; burden; intravitreal injections; mathematical model; neovascular; ranibizumab.